Study to Evaluate Adverse Events and Movement of Intravenously (IV) Infused ABBV-787 in Adult Participants With Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML)

A Phase 1 First-in-Human Study Evaluating Safety, Pharmacokinetics and Efficacy of ABBV-787 in Adult Subjects With Acute Myeloid Leukemia (AML)

Acute myeloid leukemia (AML) is the second most common type of leukemia diagnosed in adults and children, but most cases occur in adults. This study is to evaluate how safe ABBV-787 is and how it moves within the body in adult participants with relapsed/refractory (R/R) acute myeloid leukemia (AML). Adverse events and maximum tolerated dose (MTD) of ABBV-787 will be assessed.

ABBV-787 is an investigational drug being developed for the treatment of AML. Participants will receive ABBV-787 in escalating doses until the maximum tolerated dose (MTD) is determined. Approximately 60 adult participants with a diagnosis of AML will be enrolled worldwide.

Participants will receive intravenous (IV) infusions of ABBV-787 during the approximately 3 year duration a participant is followed.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests and checking for side effects.

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: ABBV-787

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health - Monash Medical Centre /ID# 253841
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Ctr /ID# 252517
• Israel
  • Jerusalem, Israel, 91120
    • Hadassah Medical Center-Hebrew University /ID# 252915
  • Tel-Aviv
    • Ramat Gan, Tel-Aviv, Israel, 5265601
      • The Chaim Sheba Medical Center /ID# 252913
    • Tel Aviv, Tel-Aviv, Israel, 6423906
      • Tel Aviv Sourasky Medical Center /ID# 252914
• Japan
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East /ID# 252519
  • Yamagata
    • Yamagata-shi, Yamagata, Japan, 990-9585
      • Yamagata University Hospital /ID# 254105
• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Yonsei University Health System Severance Hospital /ID# 253956
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03080
      • Seoul National University Hospital /ID# 252916
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 05505
      • Asan Medical Center /ID# 253955
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope /ID# 253727
    • Sacramento, California, United States, 95817
      • University of California Davis Health /ID# 252723
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University School of Medicine /ID# 252724
  • Illinois
    • Chicago, Illinois, United States, 60611-2927
      • Northwestern Memorial Hospital /ID# 252800
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical /ID# 252764
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland, Baltimore /ID# 253726
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Cancer & Hematology Centers /ID# 252803
  • New York
    • New York, New York, United States, 10065-6007
      • Memorial Sloan Kettering Cancer Center-Koch Center /ID# 252515
    • New York, New York, United States, 10065
      • Weill Cornell Medical College /ID# 252516
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-5502
      • University of Pennsylvania /ID# 252789
  • Texas
    • Austin, Texas, United States, 78704
      • St. David's South Austin Medical Center /ID# 252790
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center /ID# 252514
  • Washington
    • Seattle, Washington, United States, 98109-1024
      • Fred Hutchinson Cancer Research Center /ID# 253730
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Wisconsin Medical Center /ID# 252513

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Laboratory Criteria matching those outlined in the protocol.
• QT interval corrected for heart rate (QTc) <= 470 msec using Fridericia's correction, and no other clinically significant cardiac abnormalities.
• Documented diagnosis of non-promyelocytic acute myeloid leukemia (AML), per 2022 European Leukemia Net (ELN) criteria.
• Participants with relapsed/refractory (R/R) acute myeloid leukemia (AML) who have been treated with up to 3 prior lines of therapy and are refractory to or intolerant of all established AML therapies that are known to clearly provide clinical benefit at the judgement of the investigator.
• Must have a white blood cell (WBC) count < 25 × 10^9 /L prior to initiation of study drug (Note: Hydroxyurea or leukapheresis is permitted to meet this criterion and for use through Cycle 3 to control for hyperleukocytosis.).

Exclusion Criteria:

• Have received a CD33-targeting therapy within 3 months prior to the first dose of ABBV-787.
• Stem cell transplant within 3 months prior to first dose of study drug.
• Have received anticancer therapy including chemotherapy, radiation therapy, immunotherapy, biologic, or any investigational therapy within 14 days or 5 half-lives of the drug (whichever is shorter) prior to the first dose of ABBV-787.
• History of documented pneumonitis that required treatment with systemic steroids within the last 6 months, nor any evidence of active pneumonitis.
• Unresolved toxicity of Grade >= 2 from prior anticancer therapy, or to levels dictated in the eligibility criteria, with the exception of alopecia.
• Known active severe or poorly controlled acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ABBV-787; Participants will receive increasing doses of ABBV-787 until the maximum tolerated dose (MTD) during the 3 year treatment period.	Drug: ABBV-787; Intravenous (IV) Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events (AE)	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.	Up to Approximately 3 Years
Maximum Tolerated Dose (MTD) Based on Dose-Limiting Toxicities (DLT)	DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.	Up to approximately 28 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-time Curve (AUC) of ABBV-787	AUC of ABBV-787.	Up to Approximately 1 Year
Maximum Observed Concentration (Cmax) of ABBV-787	Cmax of ABBV-787.	Up to Approximately 1 Year
Time to Cmax (Tmax) of ABBV-787	Tmax of ABBV-787.	Up to Approximately 1 Year
Half-life (t1/2) of ABBV-787	t1/2 of ABBV-787.	Up to Approximately 1 Year
Total Antibody Concentration	Total antibody concentration	Up to Approximately 1 Year
Plasma Concentrations of Unconjugated Bromodomain and Extra-terminal Domain (BET) Degrader Payload	Plasma concentrations of unconjugated BET degrader payload.	Up to Approximately 1 Year
Antidrug Antibody (ADA)	Incidence and concentration of anti-drug antibodies.	Up to Approximately 1 Year
Neutralizing Antibody (nAb)	Incidence and concentration of neutralizing antibodies.	Up to Approximately 1 Year
Percentage of Participants Achieving Complete Remission (CR)	CR is assessed by the European Leukemia Net (ELN). ELN defines refractory disease as the inability to attain complete remission (CR) or CR with incomplete hematologic recovery (CRi) after two courses of intensive induction treatment.	Up to Approximately 1 Year
Rate of Participants Achieving CR with partial hematologic recovery (CRh)	Percentage of participants achieving CRh per ELN 2022.	Up to Approximately 1 Year
Rate of Participants Achieving CR with incomplete hematologic recovery (CRi)	Percentage of participants achieving CRi per ELN 2022.	Up to Approximately 1 Year
Rate of Participants Achieving Composite CR (CR, CRh, or CRi)	Composite CR is defined as the percentage of participants with composite CR per ELN 2022.	Up to Approximately 1 Year
Rate of Participants Achieving Partial Remission (PR)	PR is defined as the percentage of participants with PR per ELN 2022.	Up to Approximately 1 Year
Duration of Response (DOR)	DOR is defined for participants with CR, CRh, CRi, or PR as the time from the participant's initial response of CR, CRh, CRi, or PR per investigator review according to ELN 2022 criteria to disease progression or death of any cause, whichever occurs earlier.	Up to Approximately 1 Year
Number of Participants proceeding to hematopoietic stem cell transplant (HSCT)	Number of participants proceeding to HSCT	Up to Approximately 3 Years
Event-free Survival (EFS)	EFS is defined as the time from the date of the first study treatment to the date of treatment failure, or hematologic relapse from either CR, CRh, or CRi, or death from any cause, whichever occurs earlier.	Up to Approximately 3 Years
Relapse free survival (RFS)	RFS is defined for participants achieving CR, CRh, or CRi as time from the date of achievement of remission (CR, CRh, or CRi) until the date of hematologic relapse or death from any cause.	Up to Approximately 3 Years
Overall survival (OS)	OS is defined as time from first study treatment to death from any cause.	Up to Approximately 3 Years

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2023
• Primary Completion (Actual): February 25, 2025
• Study Completion (Actual): February 25, 2025

Study Registration Dates

• First Submitted: September 29, 2023
• First Submitted That Met QC Criteria: September 29, 2023
• First Posted (Actual): October 5, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 4, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; AML; ABBV-787
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: M23-477; 2023-505233-27-00 (Other Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes